3D Printed Housing Devices for Segregated Compartmental Delivery of Oral Fixed-Dose Anti-Tubercular Drugs Adopting Print and Fill Strategy.

World Health Organization (WHO) recommends the use of first-line anti-tuberculosis drugs, that is, rifampicin (RIF) and isoniazid (INH) fixed-dose combination (FDC) therapies in tuberculosis (TB) disease. The absorption of RIF from an FDC incorporates INH, and it is significantly compromised due to its reaction with INH, resulting in a severe loss of RIF under gastric stomach pH condition. Such reduction in the dose of both drugs from FDC formulations has been alleged to be one of the chief obstacles in effective TB treatment. This emphasizes a need to develop suitable cutting-edge advanced bioengineered delivery devices that can attenuate this severe problem to mitigate this chief obstacle. Therefore, we designed, prototyped, and characterized bioengineered 3D printed housing devices in the form of printed tablets adopting print and fill strategy for segregated compartmental delivery of RIF into the intestine (to avoid stomach gastric pH induced chemical degradation as alone and FDC) and INH into the stomach (no degradation observed as alone and FDC in stomach gastric pH conditions) for the desired treatment outcome against TB. Prepared 3D printed housings showed almost zero friability, enough hardness along weight variations <±3.0%. Different thermal and morphological analyses confirmed the insignificant changes in the nature of the polymer as before and after printing. The in vitro release for INH from polyvinyl alcohol mediated 3D printed housings showed almost 100% release within 2.5 h in acidic medium, whereas poly-lactic acid (PLA) mediated 3D printed housings continued to release RIF above 70% in the presence of physiological enzymes in alkaline medium for 432 h. The in vivo bioavailability assessment correlated with in vitro dissolution behavior for INH and RIF, whereas RIF did not release from 3D printed PLA housings in vivo.

3D printed hollow microneedles array using stereolithography for efficient transdermal delivery of rifampicin.

A 3D printed assembly of hollow microneedles (HMNs) array, conjoined with a reservoir void, was designed and additively manufactured using stereolithography (SLA) technology utilizing a proprietary class-I resin. The HMNs array was utilized for transdermal delivery of high molecular weight antibiotics, i.e., rifampicin (Mw 822.94 g/mol), which suffers from gastric chemical instability, low bioavailability, and severe hepatotoxicity. HMNs morphology was designed with sub-apical holes present in a quarter of the needle tip to improve its mechanical strength and integrity of the HMNs array. The HMNs array was characterized by optical microscopy and electron microscopy to ascertain the print quality and uniformity across the array. The system was also subjected to mechanical characterization for failure and penetration analyses. The ex vivo permeation and consequent transport of rifampicin across porcine skin were systematically evaluated. Finally, in vivo examinations of rifampicin administration through the microneedle reservoir system in SD rats revealed efficient penetration and desired bioavailability.